Le mercredi 15 avril 2026, Monsieur Marco MORBIDELLI, titulaire d'un Diplôme de laurea magistrale in applied and molecular biology (Università Politecnica delle Marche - Ancona - Italy) et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Monsieur Didier CATALDO et de Madame Mireille DUMOULIN.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "Inhibition of ADAM10 targeted to mesothelioma: development of a Dual Targeting protein". 

Le jury sera composé de :

Alain COLIGE (Président), Patricia LASSAUX (Secrétaire), Mireille DUMOULIN, Moreno GALLENI, Arnaud SCHERPEREEL (CHRU Lille), Cécile VINCKE (VUB).

Résumé de la thèse

Malignant Pleural Mesothelioma (MPM) is a rare but aggressive cancer primarily caused by asbestos exposure, with limited treatment options and poor prognosis. Current therapies, including chemotherapy and immune checkpoint inhibitors, have only modestly improved survival, highlighting the need for novel targeted approaches. ADAM10, a transmembrane protease, is overexpressed in MPM and associated with tumor progression, chemoresistance, and invasiveness, partly through its cleavage of N-cadherin, a regulator of cell-cell adhesion and migration. Inhibiting ADAM10 could therefore impede tumor progression. However, systemic inhibition of ADAM10 may induce adverse effects due to its physiological roles in healthy tissues.

To selectively target MPM cells, we developed a dual-targeting therapeutic protein by fusing the endogenous inhibitory prodomain of ADAM10 to a VHH antibody fragment directed against mesothelin, a surface antigen overexpressed in MPM. This construct was biochemically validated to confirm mesothelin binding and inhibition of ADAM10 activity. In vitro experiments on MPM cell lines demonstrated functional efficacy, supporting its potential as a targeted therapeutic strategy. This study provides the first evidence for using a mesothelin-targeted ADAM10 inhibitor as a novel therapeutic approach for MPM, combining specificity and efficacy while potentially minimizing systemic toxicity.